The objective of this proposal is to investigate a variety of potential factors that may increase or decrease the risk of developing prostate cancer, a disease whose etiology is poorly understood. Associations of prostate cancer with potential carcinogenic exposures (organochlorine compounds, cadmium and zinc), a susceptibility factor (GSTM1 genotype) and other risk and/or protective factors (endogenous hormones, micronutrients, fatty acids) will be examined prospectively using a nested case-control study design. The study will be conducted using prediagnostic serum collected in 1974 and plasma from 1989 in Washington County Maryland. Serum and plasma will be assayed for organochlorine compounds, zinc, cadmium, selenium, retinol, carotenoids, tocopherols, ascorbic acid, total antioxidant activity, fatty acids, endogenous hormones and GSTMI genotyping will be done using buffy coats collected in 1989. An estimated 424 men who have developed prostate cancer after donating blood will be compared with controls matched on age and gender and free of other cancers at the time of diagnosis of the case. Independent and modifying effects of these factors on the risk of prostate cancer will be examined. From the viewpoint of etiology, findings will aid in understanding the contribution of environmental organochlorine compound exposure, cadmium and zinc exposure to the development of prostate cancer and the potential inherited susceptibility to the effects of these compounds. From the viewpoint of prevention, the modifying effects of antioxidants and fatty acids on the association between organochlorine compounds and prostate cancer deserve particular attention since these are factors that are amenable to practical preventive measures.